Chronic hyperglycemia initiates a cascade of molecular events—including the accumulation of advanced glycation end products (AGEs), activation of the polyol pathway, enhanced protein kinase C (PKC) signaling, and mitochondrial dysfunction—culminating in glomerular hyperfiltration, podocyte injury, and progressive glomerular and tubulointerstitial fibrosis. This evidence concerns the gene PRRT2 and fibrosis.